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| Main Authors: | , |
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| Format: | Preprint |
| Published: |
2023
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2312.05785 |
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| _version_ | 1866914678507044864 |
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| author | Ottino-Loffler, Bertrand Victora, Gabriel |
| author_facet | Ottino-Loffler, Bertrand Victora, Gabriel |
| contents | A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in microanatomical structures called germinal centers, which form in secondary lymphoid organs upon antigen exposure. While it has been shown that the median B cell affinity dependably increases over the course of maturation, the exact logic behind this evolution remains vague. Three potential selection methods include encouraging the reproduction of high affinity cells (``birth/positive selection''), encouraging cell death in low affinity cells (``death/negative selection''), and adjusting the mutation rate based on cell affinity (``mutational selection''). While all three forms of selection would lead to a net increase in affinity, different selection methods may lead to distinct statistical dynamics. We present a tractable model of selection, and analyze proposed signatures of negative selection. Given the simplicity of the model, such signatures should be stronger here than in real systems. However, we find a number of intuitively appealing metrics -- such as preferential ancestry ratios, terminal node counts, and mutation count skewness -- are all ill-suited for detecting selection method. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2312_05785 |
| institution | arXiv |
| publishDate | 2023 |
| record_format | arxiv |
| spellingShingle | On Possible Indicators of Negative Selection in Germinal Centers Ottino-Loffler, Bertrand Victora, Gabriel Populations and Evolution Dynamical Systems A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in microanatomical structures called germinal centers, which form in secondary lymphoid organs upon antigen exposure. While it has been shown that the median B cell affinity dependably increases over the course of maturation, the exact logic behind this evolution remains vague. Three potential selection methods include encouraging the reproduction of high affinity cells (``birth/positive selection''), encouraging cell death in low affinity cells (``death/negative selection''), and adjusting the mutation rate based on cell affinity (``mutational selection''). While all three forms of selection would lead to a net increase in affinity, different selection methods may lead to distinct statistical dynamics. We present a tractable model of selection, and analyze proposed signatures of negative selection. Given the simplicity of the model, such signatures should be stronger here than in real systems. However, we find a number of intuitively appealing metrics -- such as preferential ancestry ratios, terminal node counts, and mutation count skewness -- are all ill-suited for detecting selection method. |
| title | On Possible Indicators of Negative Selection in Germinal Centers |
| topic | Populations and Evolution Dynamical Systems |
| url | https://arxiv.org/abs/2312.05785 |